Intrarenal artery infusion of hypertonic saline induces a sustained renal vasoconstriction that is most likely mediated by tubuloglomerular feedback. The purpose of this study was to investigate the contribution of angiotensin II and adenosine to this response in normal-salt and salt-deplete states. Intrarenal infusions of hypertonic saline to sodium-deplete dogs caused a renal vaso-constrictor response that was observed between 5 and 10 min into the infusion. This response was attenuated in dogs on a normal-salt diet and in salt-deplete dogs receiving captopril. Intravenous infusion of subpressor doses of angiotensin II to dogs either on a normal-salt intake or on a salt-deplete diet but receiving captopril, restored the vasoconstrictor response to hypertonic saline. The vasoconstrictor response in the presence of an angiotensin II infusion in each of these two groups of dogs was abolished by an intrarenal artery infusion of the adenosine receptor blocker, theophylline. These experiments are consistent with the hypothesis that intrarenal infusion of hypertonic saline enhances the endogenous production of adenosine and that the ability of adenosine to reduce renal blood flow is dependent on the presence of angiotensin II.